+ Expressed on all cells

Human Hematopoietic Stem and Progenitor Cell Phenotypes, Frequencies and Hierarchies
lo Lowly expressed on all or most cells

- Not expressed (or not detectable) on all or most cells

+/- Heterogenously expressed in cell population

Not known / Not applicable

Approx. Freq. in CBt HSPC Identifiers Erythroid, Mk Identifiers Cytokine Receptors Lymphoid Identifiers
Stem/Progenitor Cell Properties Lineage Potential % of MNCs % of CD34+ Lineage▲ CD34 CD38 CD45RA CD90 CD49f CD71 CD105 CD36 CD235
(GlyA) CD41 CD117
(c-Kit)
CD135
(FLT3)
CD110
(Mpl)
CD123
(IL-3Rα)
CD115 CD116 CD127
(M-CSFR) (GM-CSFRα) (IL-7Rα) CD7 CD10 CD5 CD24 CD19 CD1a CD2 icCD3ε

t10% of population have NSG mouse repopulating ability at 20 weeks16

Hematopoietic Stem Cell (HSC)16,17 t Maintains steady state hematopoiesis in humans after transplantation1 All 0.04 1.5 - + - - + + - - + + + lo - - - -

t Most have short-term repopulation ability (2 - 10 wks) in NSG mice and 0.1% have long-term NSG repopulation ability16
Multipotent Progenitor (MPP)4,12 t Significantly contributes to long-term steady state hematopoiesis in humans after transplantation1 All 0.04 2.5 - + - - - - - - + + + + - - - -

Multilymphoid Progenitor (MLP)4,8 Gives rise to all lymphoid cell types as well as some myeloid cell types Lymphoid, Monocytic, Macrophage, Dendritic 0.02 1-2 - + - + lo + +/-◆ +

t Develops from MPPs to produce all myeloid lineages

Common Myeloid Progenitor (CMP)4,13,14 t Myeloid, Erythroid, Megakaryocytic 0.15 - 0.4 24.5 - + + - - - +/- + +/- + - -
Large portion of population is primed or committed to specific lineage

Megakaryocyte-Erythroid Progenitor (MEP)3,4,8,13,14,20 Arises from CMPs, produces erythroid and megakaryocytic cells Erythroid, Megakaryocytic 0.05 - 0.3 8.0 - + lo - +/-? - - - +/-? + - + - - -

Megakaryocyte Progenitor (CFU-Mk)14,20 Originates from MEPs, or directly from HSCs and MPPs17 Megakaryocytic - + - - + - - + + - + -

Erythroid Progenitor (BFU-E)11,14,20 Represents a primitive erythroid progenitor Erythroid 0.1 - 0.35 - + + - lo + - - - + - - -

t Represents a late erythroid progenitor

Erythroid Progenitor (CFU-E)11 t Frequency is over 10-fold higher in BM than in CB or PB11
Erythroid 0.004 - 0.05 - - + + + - - + -

t Also known as “Granulocyte-Macrophage Progenitor (GMP)”

Granulocyte-Monocyte-DC Progenitor (GMDP)4,10,13 t Granulocytic, Monocytic, Dendritic (pDC, cDC) 0.05 - 0.3 10 - + + + + + + - lo - -
Gives rise to the most immature CFU-GM, CFU-G, CFU-M and dendritic cell (DC) progenitors10

t More restricted lineage potential than GMDP

Monocyte-DC Progenitor (MDP)10 t Monocytic, Dendritic (pDC, cDC) 0.6 - + + + + + + + lo -
Gives rise to CFU-M and DC, but not CFU-G progenitors10

t More restricted lineage potential than MDPs

Common Dendritic Cell Progenitor (CDP)10 t Gives Dendritic (pDC, cDC) 0.4 - + + + + + + - lo -
rise to plasmacytoid and conventional DCs

Common Lymphoid Progenitor (CLP)5,6,7,8,9,22 Gives rise to all lymphoid cell types, as well as some DCs T, B, NK, Dendritic - + -■ + - -■ -■ +e + - -

B,NK Progenitor (B,NK-P)4,7 Develops from CLPs or MLPs but does not produce T, myeloid or erythroid lineages B, NK 0.05 - + + + - + - + - -

Pro-B Progenitor15,21,22 Develops from MLPs, CLPs or B,NK-Ps B + + +/- + + +

Natural Killer Progenitor (NKP)19 Develops from MLPs, CLPs or B,NK-Ps NK - + + + - - + + -

t Committed T cell progenitor

Pre-T2 t T + + - + + + - - + + +
Develops from lymphoid progenitors (i.e. CLPs or MLPs) which seed the thymus

t Cord blood frequency estimates are variable between different donor samples and are dependent on experimental conditions (reagents, staining, conditions, flow cytometer setup, gating) and subset frequencies. Expression of some markers in other tissues (e.g, fetal liver and bone marrow) may also be different.4,10,11,13,17 ▲ Lineage markers include: CD2, CD3, CD11b, CD11c, CD14, CD16, CD19, CD24, CD56, CD66b, CD235 ◆ Not detectable in bone marrow-derived MLPs, only detectable in a fraction of cord blood-derived MLPs.4 ■ Not detectable in cord blood-derived CLPs8,9, expressed in bone marrow-derived CLPs.5,7
e Expressed in cord blood-derived CLPs8,9, not detectable in bone marrow-derived CLPs.5,22 ? MEP are heterogeneous and may include CD71- CD41- “pre-MEP” that have CFU-Mk, CFU-GM, CFU-GEMM and BFU-E/CFU-E potential, CD71+CD41- erythroid-biased MEPs and CD71+CD41+ Mk-biased MEPs.18

B: B Lymphocyte; B,NK-P: B Lymphocyte, Natural Killer-Progenitor; BFU-E: Burst-Forming Unit - Erythroid; c-Kit: KIT Proto-Oncogene Receptor Tyrosine Kinase; CB: Cord Blood; CD: Cluster of differentiation; cDC: Pre-Conventional Dendritic Cell; CDP: Common Dendritic Cell Progenitor; CFU-E: Colony-Forming Unit - Erythroid; CFU-Mk: Colony-Forming Unit - Megakaryocyte; CLP: Common Lymphoid Progenitor; CMP: Common Myeloid Progenitor; DC: Dendritic Cell; FLT3: Fms-Related Tyrosine Kinase 3; GlyA: Glycophorin A; GM-CSFRα: Granulocyte-Macrophage Colony-Stimulating Factor Receptor Alpha Chain; GMDP: Granulocyte-Monocyte-Dendritic Cell Progenitor;
GMP: Granulocyte-Macrophage Progenitor; HSC: Hematopoietic Stem Cell; HSPC: Hematopoietic Stem and Progenitor Cell; ic: Intracellular; IL-3Rα: Interleukin-3 Receptor Alpha Chain; IL-7Rα: Interleukin-7 Receptor Alpha Chain; IL: Interleukin; Lin: Lineage; M-CSFR: Macrophage Colony-Stimulating Factor Receptor; MDP: Monocyte-Dendritic Cell Progenitor; MEP: Megakaryocyte-Erythroid Progenitor; Mk: Megakaryocyte; MLP: Multilymphoid Progenitor; Mpl: Myeloproliferative Leukemia/Thrombopoietin Receptor; MPP: Multipotent Progenitor; NK: Natural Killer; NKP: Natural Killer Progenitor; NSG: Non-Obese Diabetic (NOD) Severe Combined Immunodeficiency (SCID) Gamma;
pDC: Pre-Plasmacytoid Dendritic Cell; T: T Lymphocyte

Progenitor Subset Hierarchy Hematopoietic Cell Compartments and Assays for Their Identification References
1. Biasco L et al. (2016) Cell Stem Cell 19(1): 107-19.
2. Blom B and Spits H (2006) Ann Rev of Immunol 24: 287-320.
3. Debili N et al. (1996) Blood 88(4): 1284-96.
HSC 4. Doulatov S et al. (2010) Nat Immunol 11(7): 585-93.
5. Galy A et al. (1995) Immunity 3(4): 459-73.
MPP Hematopoietic Stem Cells (HSCs) Transplantation Assays in Immunodeficient Mice 6. Haddad R et al. (2004) Blood 104(13): 3918-26.
(Competitive Repopulating Unit (CRU) Assays) 7. Haddad R et al. (2006) Immunity 24(2): 217-30.
MLP 8. Hao QL et al. (2001) Blood 97(12): 3683-90.
9. Hoebeke I et al. (2007) Leuekmia 21(2): 311-9.
CMP 10. Lee J et al. (2015) J Exp Med 212(3): 385-99.
11. Li J et al. (2014) Blood 124(24): 3636-45.
MEP Long-Term Culture-Initiating Cell (LTC-IC) Assays with MyeloCult™ 12. Majeti R et al. (2007) Cell Stem Cell 1(6): 635-45.
Multipotent Progenitors (MPPs) Expansion and 13. Manz MG et al. (2002) Proc Natl Acad Sci 99(18): 11872-7.
CFU-Mk Differentiation Cultures 14. Mori Y et al. (2015) Proc Natl Acad Sci 112(31): 9638-43.
CFU - Granulocyte, Erythrocyte, Macrophage with StemSpan™
15. Nodland SE et al. (2011) Blood 118(8): 2116-27.

and Megakaryocyte (CFU-GEMM) 16. Notta F et al. (2011) Science 333(6039): 218-21.
17. Notta F et al. (2016) Science 351(6269): 139.
BFU-E 18. Psaila B et al. (2016) Genome Biology 17: 83.
CFU - Granulocyte/Macrophage (CFU-GM) Colony-Forming 19. Renoux VM et al. (2015) Immunity 43(2): 394-407.
CFU-E Lineage-Committed Progenitors CFU- Granulocyte (CFU-G) Unit (CFU) Assays 20. Sanada C et al. (2016) Blood 128(7): 923-33.
CFU - Macrophage (CFU-M) with MethoCult™ 21. Sanz I and Lee F (2010) Nat Rev Rheumatol 6(6): 326-37.
CFU - Megakaryocyte (CFU-Mk) 22. Six EM et al. (2007) J Exp Med 204(13): 3085-93.
GMDP CFU - Erythroid (CFU-E)
Burst-Forming Unit - Erythroid (BFU-E)
MDP

CDP
Precursor Cells
CLP

B,NK-P
Immunophenotyping
Pro-B Functional Tests
Morphological Stains
NKP
Mature Cells
Pre-T

Lineage Potential

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