Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), Stanford University, Stanford, CA 94305, USA.
Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Stem Cell Reports. 2014 Mar 20;2(4):457-72. doi: 10.1016/j.stemcr.2014.02.001. eCollection 2014 Apr 8.
Hematopoiesis in the embryo proceeds in a series of waves, with primitive erythroid-biased waves succeeded by definitive waves, within which the properties of hematopoietic stem cells (multilineage potential, self-renewal, and engraftability) gradually arise. Whereas self-renewal and engraftability have previously been examined in the embryo, multipotency has not been thoroughly addressed, especially at the single-cell level or within well-defined populations. To identify when and where clonal multilineage potential arises during embryogenesis, we developed a single-cell multipotency assay. We find that, during the initiation of definitive hematopoiesis in the embryo, a defined population of multipotent, engraftable progenitors emerges that is much more abundant within the yolk sac (YS) than the aorta-gonad-mesonephros (AGM) or fetal liver. These experiments indicate that multipotent cells appear in concert within both the YS and AGM and strongly implicate YS-derived progenitors as contributors to definitive hematopoiesis.
胚胎中的造血过程是一系列波浪式的进展,原始红系偏向的波次之后是确定的波次,在这个过程中造血干细胞的特性(多能性、自我更新和植入能力)逐渐出现。虽然自我更新和植入能力以前在胚胎中已经被研究过,但多能性尚未得到彻底解决,尤其是在单细胞水平或在明确界定的群体中。为了确定在胚胎发生过程中何时以及何处出现克隆多能性,我们开发了一种单细胞多能性测定法。我们发现,在胚胎中确定的造血发生开始时,出现了一个定义明确的多能、可植入祖细胞群体,其在卵黄囊(YS)中的丰度远远高于主动脉-性腺-中肾(AGM)或胎肝。这些实验表明,多能细胞同时出现在 YS 和 AGM 中,并强烈暗示 YS 衍生的祖细胞是确定造血的贡献者。